Vitamin E suppresses enhancement of factor VIII-dependent thrombin generation by systemic hypoxia.
OBJECTIVE
Increased thrombin activity is an essential component of hemostatic reactions. This study elucidates how various hypoxic interventions impact endogenous thrombin generation (TG) after treatment with/without lipophilic antioxidant vitamin E.


METHODS
Twenty-four healthy sedentary men were randomly assigned to vitamin E (n=12) and placebo (n=12) groups. These subjects were randomly exposed to 12% (severe hypoxia), 15% (moderate hypoxia), 18% (light hypoxia), and 21% (normoxia) O(2) for 2 hours in a normobaric hypoxia chamber. A novel calibrated, automated thrombinography approach was used to measure TG in plasma.


RESULTS
In the placebo group, severe hypoxia enhanced plasma FVIII level/activity and TG, which was accompanied by increased urinary 15-F2t-8-isoprostane level and decreased plasma total antioxidant content and superoxide dismutase activity. However, depletion of FVIII by incubation with anti-FVIII antibodies in plasma suppressed enhancement of TG by severe hypoxia. After administration of 1000 IU vitamin E, severe hypoxia did not significantly alter urinary 15-F(2t)-8-isoprostane level and plasma total antioxidant content, superoxide dismutase activity, FVIII level/activity, or TG. Moreover, redox status, FVIII level/activity, and TG were constant in response to moderate hypoxia, light hypoxia, and normoxia in the placebo and vitamin E groups.


CONCLUSIONS
We conclude that severe hypoxia promotes FVIII-dependent TG, likely by elevating oxidative stress; this hypoxic effect was ameliorated by pretreatment with vitamin E.
Wang
Jong-Shyan
JS
Graduate Institute of Rehabilitation Science, Chang Gung University, Kwei-Shan, Tao-Yuan, Taiwan. s5492@mail.cgu.edu.tw
Cheng
Mei-Ling
ML
Yen
Hsiu-Chuan
HC
Lou
Bih-Show
BS
Liu
Huang-Chun
HC
D000328:Adult; D000975:Antioxidants / Q000494:pharmacology*; D001777:Blood Coagulation / Q000187:drug effects; D003404:Creatinine / Q000378:metabolism; D005169:Factor VIII / Q000502:physiology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D028421:Isoprostanes / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D013482:Superoxide Dismutase / Q000378:metabolism; D013917:Thrombin / Q000096:biosynthesis*; D014810:Vitamin E / Q000494:pharmacology*
D000975:Antioxidants; D028421:Isoprostanes; D014810:Vitamin E; D005169:Factor VIII; D003404:Creatinine; D013482:Superoxide Dismutase; D013917:Thrombin